Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01361464
First received: May 24, 2011
Last updated: March 19, 2015
Last verified: February 2015
  Purpose

This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Acute Megakaryoblastic Leukemia
Adult Acute Monoblastic Leukemia
Adult Acute Monocytic Leukemia
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With Maturation
Adult Acute Myeloid Leukemia With Minimal Differentiation
Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1
Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL
Adult Acute Myeloid Leukemia Without Maturation
Adult Acute Myelomonocytic Leukemia
Adult Erythroleukemia
Adult Pure Erythroid Leukemia
Alkylating Agent-Related Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: Tipifarnib
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete Remission (CR) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]
    Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.


Secondary Outcome Measures:
  • Median Overall Survival (OS) [ Time Frame: From first treatment through follow up period, an expected average of 12 months ] [ Designated as safety issue: No ]
    Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).

  • Median 1-Year Survival Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.

  • Number of Participants With Relapse Free Survival [ Time Frame: 7 months ] [ Designated as safety issue: No ]
    Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.


Enrollment: 21
Study Start Date: May 2011
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: Tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.

SECONDARY OBJECTIVES:

I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.

III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.

OUTLINE: This is a multicenter study.

Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.

After completion of study therapy, patients are followed up every 30 days.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated acute myeloid leukemia (AML) (de novo or secondary)

    • No diagnosis of acute promyelocytic leukemia (APL)
  • Deemed unsuitable for or refuses standard induction chemotherapy
  • RASGRP1:APTX ratio >= 5, through bone marrow screening
  • No patients with known leukemic involvement of the central nervous system
  • ECOG performance status =< 2
  • No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
  • Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)
  • Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
  • ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
  • Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • No symptomatic neuropathy of grade 2 or worse
  • No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy AND with a CD4 cell count >= 400/mm^3 are eligible
  • No other concurrent cytotoxic or biologic antileukemic therapy
  • No patients who are receiving any other investigational agents
  • Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated

    • If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01361464

Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Investigators
Principal Investigator: Jeffrey Lancet Moffitt Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01361464     History of Changes
Obsolete Identifiers: NCT01364038
Other Study ID Numbers: NCI-2011-02589, NCI-2011-02589, 16572, CDR0000699713, 8977, 8977, P30CA076292, N01CM00071, U01CA070095, N01CM00100
Study First Received: May 24, 2011
Results First Received: November 15, 2013
Last Updated: March 19, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Tipifarnib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015